Our precious pooches can carry one of the strangest diseases known to exist—a sexually transmitted form of cancer that’s jumped from host to host for thousands of years. Now, a large group of researchers say they’ve unpacked the evolutionary history of this disease, all the way back to the first dogs in which it arose. And it’s even weirder than expected.
Most cancers—the mutated, uncontrollable, and harmful growth of a body’s cells—are unique. Sure, if you and someone else both have a specific type of breast cancer, those cells will behave in similar ways. But your cancer cells belong to you alone, and they’ll be noticeably different from the cancer cells of another person. You also can’t really infect someone with your cancer, mostly because our immune system can usually recognize and destroy foreign human cells.
That said, there have been rare examples of cancer transmission in humans. These have largely happened to people with poor immune systems who got organ transplants from a donor with cancer, or from mother to child in the womb. But they’re short-lived, isolated cases, with the cancer never spreading further to others.
However, some cancers in some animals have been able to take on an infectious life on their own, having “learned” how to escape their original hosts and spread freely throughout the population like a bacteria or virus does. One of these immortal rogue agents is known as the canine transmissible venereal tumor, or CTVT. And like the name indicates, it’s sexually transmitted.
For their new study, published Thursday in Science, the authors studied the genetics of nearly 550 tumors taken from dogs in 43 countries between 2003 to 2016. Like every other thing that could be considered “living,” cancers acquire mutations and evolve over time. So by studying and comparing the mutations accumulated by these tumors, the team constructed a likely evolutionary tree for CTVT.
The study wasn’t meant to pin down exactly where and when CTVT emerged, lead author Adrian Baez-Ortega, a bioengineer and PhD student at the University of Cambridge in the UK, told Gizmodo in an email. But the team did find evidence that it first spawned among dogs in Asia sometime between 4,000 and 8,500 years ago. That roughly agrees with the results of a study last year, which theorized that CTVT was the only remaining genetic legacy of the first dogs that migrated from Asia to the Americas during that time period.
Baez-Ortega and his team were more interested in tracking the genetic journey CTVT had taken since it broke free from its confinement, particularly when it started to rapidly spread around the world in the past thousand years or so. And there they found some truly peculiar differences between it and other cancers.
“Our results show that, for at least the last 1,000–2,000 years, CTVT has been evolving differently than human cancers do,” he said. “Whereas human cancers evolve thanks to the continuous acquisition of mutations which confer an advantage on some of the cancer cells, making them fitter to their environment (this is known as ‘positive selection’), CTVT shows no evidence of this. We conclude that CTVT has really ceased to evolve in any particular ‘direction,’ and so its evolution is largely undirected or, if you like, ‘random’ (this is known as ‘genetic drift’).”
More plainly, CTVT has likely been stuck in neutral for millennia, accumulating mutations that haven’t helped or harmed its chances of survival. The team didn’t even find evidence that CTVT has evolved to better resist current chemotherapy treatments, though it’s possible this trend could show up in the future (there have been anecdotal reports of resistance in some areas of the world).
Over the long term, this inertness could doom CTVT. When genetic drift happens in a population, it often means the population won’t be able to adapt to a changing world. And eventually, it might just die out entirely.
But that expiration date probably won’t come for tens of thousands of years, Baez-Ortega noted. We do know that CTVT has been declining in areas of the world where dogs are kept almost entirely indoors as pets, such as the U.S. and UK, thanks to spaying and neutering policies and less sexual contact with free-roaming dogs in the wild. But it still remains endemic in at least 90 countries.
One mystery left unsolved by the team is exactly how CTVT managed to become transmissible in the first place.
“We didn’t find any indications of CTVT being an unusual cancer, genetically speaking,” Baez-Ortega said. “The mutations that we think were probably implicated in CTVT’s emergence and early evolution are very common and well-known cancer ‘driver’ mutations that are seen in many human cancers, and we did not find anything that points to an obvious special mechanism for transmissibility.”
What that means, he added, is that there’s no simple explanation for why these cancers became infectious. They obviously had to develop ways to consistently fend off the immune system, but they also likely got lucky. In the case of CTVT, it might have been able to spread because it formed so close to the genitals, making for a convenient route of transmission, and because dogs aren’t very genetically different from each other. That low genetic diversity probably made it easier for the cancer to survive a new host.
There are still more genetic clues to ferret out from the earliest days of CTVT, though, which the team hopes to study next.
“We would like to look into the early history of CTVT in more detail and find out how its early genome looked like, and how it changed, during its first years and decades of evolution,” Baez-Ortega said. “We are also very interested in learning more about the mechanisms by which these tumors are able to counteract the immune system in so many different kinds of dogs.”